项目来源

美国卫生和人类服务部基金(HHS)

项目主持人

WONG, RENEE P

项目受资助机构

STANFORD UNIVERSITY

项目编号

5R24HL117756-05

立项年度

2018

立项时间

未公开

研究期限

未知 / 未知

项目级别

国家级

受资助金额

1699925.00美元

学科

Biotechnology; Cardiovascular; Clinical Research; Congenital Heart Disease; Genetics; Health Disparities; Heart Disease; Human Genome; Minority Health; Orphan Drug; Pediatric; Pediatric Cardiomyopathy; Rare Diseases; Stem Cell Research; Stem Cell Research - Induced Pluripotent Stem Cell; Stem Cell Research - Induced Pluripotent Stem Cell - Human; Women's Health;

学科代码

未公开

基金类别

Other Research Related

关键词

未公开

参与者

BUSTAMANTE, CARLOS DANIEL; SNYDER, MICHAEL P.; WU, JOSEPH C.

参与机构

NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

项目标书摘要：DESCRIPTION (provided by applicant): Familial dilated cardiomyopathy (DCM) and familial hypertrophic cardiomyopathy (HOM) are considered the two most common causes of inherited cardiovascular diseases. Previously, it has been difficult to study these diseases in human models because of limited access to human cardiomyocytes and difficulty growing them. With the discovery of human induced pluripotent stem cells (iPSCs) and the increased efficiency and reproducibility of differentiating them into beating cardiomyocytes (iPSC-CMs), the landscape has dramatically changed. For the first time, it is now possible to create patient-specific and disease-specific cell lines to improve our understanding of the molecular mechanisms of DCM and HCM. Hence the major goals of this multidisciplinary R24 Resource-Related Research Project are (i) generation, (ii) characterization, (iii) sequencing, and (iv) distribution of cardiac iPSC lines. Over the next 5 years, we plan to create an iPSC bank of 600 lines derived from control individuals, HCM patients, and DCM patients. To accomplish these goals, we have assembled a truly collaborative team of investigators with expertise in cardiovascular medicine, iPSC biology, developmental biology, next generation sequencing (NGS) technology, population genetics, biomedical informatics, large-scale database repository, and business development. We propose the following 4 Specific Aims over the next 5 years: Aim 1: To generate 600 iPSC lines from controls, DCM, and HCM patients. Aim 2: To evaluate drug safety screening using iPSCs (clinical trial in a petri dish). Aim 3: To obtain genotype-phenotype information using DNA-seq and RNA-seq. Aim 4: To distribute IPSC lines and their genotype-phenotype data to academic community. In summary, we believe this R24 will address a national need and fulfill NHLBI's strategic vision of creating a novel biorepository (iPSC-genotype-phenotype) that is valuable to the broader scientific community. Given our expertise and track record, we are confident we can deliver on these milestones.